1932

Abstract

The question of how noncoding RNAs are involved in Polycomb group (PcG) and Trithorax group (TrxG) regulation has been on an extraordinary journey over the last three decades. Favored models have risen and fallen, and healthy debates have swept back and forth. The field has recently reached a critical mass of compelling data that throws light on several previously unresolved issues. The time is ripe for a fruitful combination of these findings with two other long-running avenues of research, namely the biochemical properties of the PcG/TrxG system and the application of theoretical mathematical models toward an understanding of the system's regulatory properties. I propose that integrating our current knowledge of noncoding RNA into a quantitative biochemical and theoretical framework for PcG and TrxG regulation has the potential to reconcile several apparently conflicting models and identifies fascinating questions for future research.

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2017-11-27
2024-06-18
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Literature Cited

  1. Agger K, Cloos PA, Christensen J, Pasini D, Rose S. 1.  et al. 2007. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449:731–34 [Google Scholar]
  2. An S, Yeo KJ, Jeon YH, Song J-J. 2.  2011. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J. Biol. Chem. 286:8369–74 [Google Scholar]
  3. Angel A, Song J, Dean C, Howard M. 3.  2011. A Polycomb-based switch underlying quantitative epigenetic memory. Nature 476:105–8 [Google Scholar]
  4. Angel A, Song J, Yang H, Questa JI, Dean C, Howard M. 4.  2015. Vernalizing cold is registered digitally at FLC. PNAS 112:4146–51 [Google Scholar]
  5. Bae E, Calhoun VC, Levine M, Lewis EB, Drewell RA. 5.  2002. Characterization of the intergenic RNA profile at abdominal-A and Abdominal-B in the Drosophila bithorax complex. PNAS 99:16847–52 [Google Scholar]
  6. Bantignies F, Goodman RH, Smolik SM. 6.  2000. Functional interaction between the coactivator Drosophila CREB-binding protein and ASH1, a member of the trithorax group of chromatin modifiers. Mol. Cell. Biol. 20:9317–30 [Google Scholar]
  7. Bauer M, Trupke J, Ringrose L. 7.  2016. The quest for mammalian Polycomb response elements: Are we there yet?. Chromosoma 125:471–96 [Google Scholar]
  8. Baymaz HI, Fournier A, Laget S, Ji Z, Jansen PW. 8.  et al. 2014. MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain. Proteomics 14:2179–89 [Google Scholar]
  9. Beltran M, Yates CM, Skalska L, Dawson M, Reis FP. 9.  et al. 2016. The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res 26:896–907 [Google Scholar]
  10. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ. 10.  et al. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–26 [Google Scholar]
  11. Bernstein E, Duncan EM, Masui O, Gil J, Heard E, Allis CD. 11.  2006. Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol. Cell. Biol. 26:2560–69 [Google Scholar]
  12. Berry S, Dean C. 12.  2015. Environmental perception and epigenetic memory: mechanistic insight through FLC. Plant J 83:133–48 [Google Scholar]
  13. Berry S, Dean C, Howard M. 13.  2017. Noise filtering by Polycomb target genes requires slow chromatin dynamics. Cell Syst 4:445–57.e8 [Google Scholar]
  14. Berry S, Hartley M, Olsson TS, Dean C, Howard M. 14.  2015. Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance. eLife 4:e07205 [Google Scholar]
  15. Bintu L, Yong J, Antebi YE, McCue K, Kazuki Y. 15.  et al. 2016. Dynamics of epigenetic regulation at the single-cell level. Science 351:720–24 [Google Scholar]
  16. Blackledge NP, Rose NR, Klose RJ. 16.  2015. Targeting Polycomb systems to regulate gene expression: modifications to a complex story. Nat. Rev. Mol. Cell Biol. 16:643–49 [Google Scholar]
  17. Bowen NJ, Fujita N, Kajita M, Wade PA. 17.  2004. Mi-2/NuRD: multiple complexes for many purposes. Biochim. Biophys. Acta 1677:52–57 [Google Scholar]
  18. Box GEP, Draper NR. 18.  1987. Empirical Model-Building and Response Surfaces New York: John Wiley & Sons [Google Scholar]
  19. Brockdorff N. 19.  2013. Noncoding RNA and Polycomb recruitment. RNA 19:429–42 [Google Scholar]
  20. Buzin CH, Mann JR, Singer-Sam J. 20.  1994. Quantitative RT-PCR assays show Xist RNA levels are low in mouse female adult tissue, embryos and embryoid bodies. Development 120:3529–36 [Google Scholar]
  21. Cabili MN, Dunagin MC, McClanahan PD, Biaesch A, Padovan-Merhar O. 21.  et al. 2015. Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biol 16:20 [Google Scholar]
  22. Cao R, Tsukada Y, Zhang Y. 22.  2005. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol. Cell 20:845–54 [Google Scholar]
  23. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H. 23.  et al. 2002. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298:1039–43 [Google Scholar]
  24. Cech TR, Steitz JA. 24.  2014. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157:77–94 [Google Scholar]
  25. Cerase A, Smeets D, Tang YA, Gdula M, Kraus F. 25.  et al. 2014. Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy. PNAS 111:2235–40 [Google Scholar]
  26. Chan CS, Rastelli L, Pirrotta V. 26.  1994. A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression. EMBO J 13:2553–64 [Google Scholar]
  27. Christophersen NS, Helin K. 27.  2010. Epigenetic control of embryonic stem cell fate. J. Exp. Med. 207:2287–95 [Google Scholar]
  28. Cifuentes-Rojas C, Hernandez AJ, Sarma K, Lee JT. 28.  2014. Regulatory interactions between RNA and polycomb repressive complex 2. Mol. Cell 55:171–85 [Google Scholar]
  29. Clark SJ, Lee HJ, Smallwood SA, Kelsey G, Reik W. 29.  2016. Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity. Genome Biol 17:72 [Google Scholar]
  30. Comet I, Riising EM, Leblanc B, Helin K. 30.  2016. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat. Rev. Cancer 16:803–10 [Google Scholar]
  31. Cooper S, Dienstbier M, Hassan R, Schermelleh L, Sharif J,. 30a.  2014. Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep. 7:1456–70 [Google Scholar]
  32. Creppe C, Palau A, Malinverni R, Valero V, Buschbeck M. 31.  2014. A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation. PLOS Genet 10:e1004851 [Google Scholar]
  33. Cumberledge S, Zaratzian A, Sakonju S. 32.  1990. Characterization of two RNAs transcribed from the cis-regulatory region of the abd-A domain within the Drosophila bithorax complex. PNAS 87:3259–63 [Google Scholar]
  34. Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V. 33.  2002. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 111:185–96 [Google Scholar]
  35. da Rocha ST, Boeva V, Escamilla-Del-Arenal M, Ancelin K, Granier C. 34.  et al. 2014. Jarid2 is implicated in the initial Xist-induced targeting of PRC2 to the inactive X chromosome. Mol. Cell 53:301–16 [Google Scholar]
  36. da Rocha ST, Heard E. 35.  2017. Novel players in X inactivation: insights into Xist-mediated gene silencing and chromosome conformation. Nat. Struct. Mol. Biol. 24:197–204 [Google Scholar]
  37. Davidovich C, Cech TR. 36.  2015. The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2. RNA 21:2007–22 [Google Scholar]
  38. Davidovich C, Wang X, Cifuentes-Rojas C, Goodrich KJ, Gooding AR. 37.  et al. 2015. Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA. Mol. Cell 57:552–58 [Google Scholar]
  39. Davidovich C, Zheng L, Goodrich KJ, Cech TR. 38.  2013. Promiscuous RNA binding by Polycomb repressive complex 2. Nat. Struct. Mol. Biol. 20:1250–57 [Google Scholar]
  40. de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M. 39.  et al. 2004. Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev. Cell 7:663–76 [Google Scholar]
  41. Deng W, Buzas DM, Ying H, Robertson M, Taylor J. 40.  et al. 2013. Arabidopsis Polycomb Repressive Complex 2 binding sites contain putative GAGA factor binding motifs within coding regions of genes. BMC Genom 14:593 [Google Scholar]
  42. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S. 41.  et al. 2012. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–89 [Google Scholar]
  43. Devaiah BN, Lewis BA, Cherman N, Hewitt MC, Albrecht BK. 42.  et al. 2012. BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA polymerase II carboxy-terminal domain. PNAS 109:6927–32 [Google Scholar]
  44. Di Croce L, Helin K. 43.  2013. Transcriptional regulation by Polycomb group proteins. Nat. Struct. Mol. Biol. 20:1147–55 [Google Scholar]
  45. Dietrich N, Lerdrup M, Landt E, Agrawal-Singh S, Bak M. 44.  et al. 2012. REST-mediated recruitment of polycomb repressor complexes in mammalian cells. PLOS Genet 8:e1002494 [Google Scholar]
  46. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T. 45.  et al. 2012. Landscape of transcription in human cells. Nature 489:101–8 [Google Scholar]
  47. Dodd DW, Gagnon KT, Corey DR. 46.  2013. Digital quantitation of potential therapeutic target RNAs. Nucleic Acid Ther 23:188–94 [Google Scholar]
  48. Dodd IB, Micheelsen MA, Sneppen K, Thon G. 47.  2007. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129:813–22 [Google Scholar]
  49. Dodd IB, Sneppen K. 48.  2011. Barriers and silencers: a theoretical toolkit for control and containment of nucleosome-based epigenetic states. J. Mol. Biol. 414:624–37 [Google Scholar]
  50. Eissenberg JC, Lee MG, Schneider J, Ilvarsonn A, Shiekhattar R, Shilatifard A. 49.  2007. The trithorax-group gene in Drosophila little imaginal discs encodes a trimethylated histone H3 Lys4 demethylase. Nat. Struct. Mol. Biol. 14:344–46 [Google Scholar]
  51. Endoh M, Endo TA, Endoh T, Isono K, Sharif J. 50.  et al. 2012. Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. PLOS Genet 8:e1002774 [Google Scholar]
  52. Erokhin M, Elizar'ev P, Parshikov A, Schedl P, Georgiev P, Chetverina D. 51.  2015. Transcriptional read-through is not sufficient to induce an epigenetic switch in the silencing activity of Polycomb response elements. PNAS 112:14930–35 [Google Scholar]
  53. Eskeland R, Leeb M, Grimes GR, Kress C, Boyle S. 52.  et al. 2010. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol. Cell 38:452–64 [Google Scholar]
  54. Farcas AM, Blackledge NP, Sudbery I, Long HK, McGouran JF. 53.  et al. 2012. KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands. eLife 1:e00205 [Google Scholar]
  55. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. 54.  2003. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 17:1870–81 [Google Scholar]
  56. Francis NJ, Kingston RE, Woodcock CL. 55.  2004. Chromatin compaction by a polycomb group protein complex. Science 306:1574–77 [Google Scholar]
  57. Francis NJ, Saurin AJ, Shao Z, Kingston RE. 56.  2001. Reconstitution of a functional core polycomb repressive complex. Mol. Cell 8:545–56 [Google Scholar]
  58. Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ. 57.  2006. Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol. Cell. Biol. 26:6880–89 [Google Scholar]
  59. Geisler SJ, Paro R. 58.  2015. Trithorax and Polycomb group-dependent regulation: a tale of opposing activities. Development 142:2876–87 [Google Scholar]
  60. Gregory GD, Vakoc CR, Rozovskaia T, Zheng X, Patel S. 59.  et al. 2007. Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol. Cell. Biol. 27:8466–79 [Google Scholar]
  61. Grossniklaus U, Paro R. 60.  2014. Transcriptional silencing by Polycomb-group proteins. Cold Spring Harb. Perspect. Biol. 6:a019331 [Google Scholar]
  62. Guenzl PM, Barlow DP. 61.  2012. Macro lncRNAs: a new layer of cis-regulatory information in the mammalian genome. RNA Biol 9:731–41 [Google Scholar]
  63. Guil S, Soler M, Portela A, Carrere J, Fonalleras E. 62.  et al. 2012. Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat. Struct. Mol. Biol. 19:664–70 [Google Scholar]
  64. Haerter JO, Lovkvist C, Dodd IB, Sneppen K. 63.  2014. Collaboration between CpG sites is needed for stable somatic inheritance of DNA methylation states. Nucleic Acids Res 42:2235–44 [Google Scholar]
  65. Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS. 64.  et al. 2008. A model for transmission of the H3K27me3 epigenetic mark. Nat. Cell Biol. 10:1291–300 [Google Scholar]
  66. He J, Kallin EM, Tsukada Y, Zhang Y. 65.  2008. The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat. Struct. Mol. Biol. 15:1169–75 [Google Scholar]
  67. Hekimoglu B, Ringrose L. 66.  2009. Non-coding RNAs in polycomb/trithorax regulation. RNA Biol 6:129–37 [Google Scholar]
  68. Hekimoglu-Balkan B, Aszodi A, Heinen R, Jaritz M, Ringrose L. 67.  2012. Intergenic Polycomb target sites are dynamically marked by non-coding transcription during lineage commitment. RNA Biol 9:314–25 [Google Scholar]
  69. Heo JB, Sung S. 68.  2011. Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science 331:76–79 [Google Scholar]
  70. Herzog VA, Lempradl A, Trupke J, Okulski H, Altmutter C. 69.  et al. 2014. A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element. Nat. Genet. 46:973–81 [Google Scholar]
  71. Hogga I, Karch F. 70.  2002. Transcription through the iab-7 cis-regulatory domain of the bithorax complex interferes with maintenance of Polycomb-mediated silencing. Development 129:4915–22 [Google Scholar]
  72. Hogness DS, Lipshitz HD, Beachy PA, Peattie DA, Saint RB. 71.  et al. 1985. Regulation and products of the Ubx domain of the bithorax complex. Cold Spring Harb. Symp. Quant. Biol. 50:181–94 [Google Scholar]
  73. Holdt LM, Hoffmann S, Sass K, Langenberger D, Scholz M. 72.  et al. 2013. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLOS Genet 9:e1003588 [Google Scholar]
  74. Hong S, Cho YW, Yu LR, Yu H, Veenstra TD, Ge K. 73.  2007. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. PNAS 104:18439–44 [Google Scholar]
  75. Islam S, Zeisel A, Joost S, La Manno G, Zajac P. 74.  et al. 2014. Quantitative single-cell RNA-seq with unique molecular identifiers. Nat. Methods 11:163–66 [Google Scholar]
  76. Jung HR, Pasini D, Helin K, Jensen ON. 75.  2010. Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse embryonic stem cells reveals distinct, dynamic post-translational modifications at Lys-27 and Lys-36. Mol. Cell. Proteom. 9:838–50 [Google Scholar]
  77. Kalb R, Latwiel S, Baymaz HI, Jansen PW, Muller CW. 76.  et al. 2014. Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression. Nat. Struct. Mol. Biol. 21:569–71 [Google Scholar]
  78. Kaneko S, Bonasio R, Saldana-Meyer R, Yoshida T, Son J. 77.  et al. 2014. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol. Cell 53:290–300 [Google Scholar]
  79. Kaneko S, Son J, Bonasio R, Shen SS, Reinberg D. 78.  2014. Nascent RNA interaction keeps PRC2 activity poised and in check. Genes Dev 28:1983–88 [Google Scholar]
  80. Kaneko S, Son J, Shen SS, Reinberg D, Bonasio R. 79.  2013. PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat. Struct. Mol. Biol. 20:1258–64 [Google Scholar]
  81. Kanhere A, Viiri K, Araujo CC, Rasaiyaah J, Bouwman RD. 80.  et al. 2010. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell 38:675–88 [Google Scholar]
  82. Kassis JA, Brown JL. 81.  2013. Polycomb group response elements in Drosophila and vertebrates. Adv. Genet. 81:83–118 [Google Scholar]
  83. Kavi HH, Birchler JA. 82.  2009. Drosophila KDM2 is a H3K4me3 demethylase regulating nucleolar organization. BMC Res. Notes 2:217 [Google Scholar]
  84. Kellner WA, Van Bortle K, Li L, Ramos E, Takenaka N, Corces VG. 83.  2013. Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites. Nucleic Acids Res 41:9274–83 [Google Scholar]
  85. Khalil AM, Guttman M, Huarte M, Garber M, Raj A. 84.  et al. 2009. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. PNAS 106:11667–72 [Google Scholar]
  86. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC. 85.  et al. 2011. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–85 [Google Scholar]
  87. Klose RJ, Cooper S, Farcas AM, Blackledge NP, Brockdorff N. 86.  2013. Chromatin sampling–an emerging perspective on targeting polycomb repressor proteins. PLOS Genet 9:e1003717 [Google Scholar]
  88. Kockmann T, Gerstung M, Schlumpf T, Xhinzhou Z, Hess D. 87.  et al. 2013. The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila. Genome Biol 14:R18 [Google Scholar]
  89. Krajewski WA, Nakamura T, Mazo A, Canaani E. 88.  2005. A motif within SET-domain proteins binds single-stranded nucleic acids and transcribed and supercoiled DNAs and can interfere with assembly of nucleosomes. Mol. Cell. Biol. 25:1891–99 [Google Scholar]
  90. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D. 89.  2002. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev 16:2893–905 [Google Scholar]
  91. Lagarou A, Mohd-Sarip A, Moshkin YM, Chalkley GE, Bezstarosti K. 90.  et al. 2008. dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing. Genes Dev 22:2799–810 [Google Scholar]
  92. Lambert TJ, Waters JC. 91.  2017. Navigating challenges in the application of superresolution microscopy. J. Cell Biol. 216:53–63 [Google Scholar]
  93. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK. 92.  et al. 2007. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449:689–94 [Google Scholar]
  94. Lee MG, Villa R, Trojer P, Norman J, Yan KP. 93.  et al. 2007. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318:447–50 [Google Scholar]
  95. Lee N, Zhang J, Klose RJ, Erdjument-Bromage H, Tempst P. 94.  et al. 2007. The trithorax-group protein Lid is a histone H3 trimethyl-Lys4 demethylase. Nat. Struct. Mol. Biol. 14:341–43 [Google Scholar]
  96. Lempradl A, Ringrose L. 95.  2008. How does noncoding transcription regulate Hox genes?. BioEssays 30:110–21 [Google Scholar]
  97. Levi V, Gratton E. 96.  2007. Exploring dynamics in living cells by tracking single particles. Cell Biochem. Biophys. 48:1–15 [Google Scholar]
  98. Lipshitz HD, Peattie DA, Hogness DS. 97.  1987. Novel transcripts from the Ultrabithorax domain of the bithorax complex. Genes Dev 1:307–22 [Google Scholar]
  99. Lovkvist C, Dodd IB, Sneppen K, Haerter JO. 98.  2016. DNA methylation in human epigenomes depends on local topology of CpG sites. Nucleic Acids Res 44:5123–32 [Google Scholar]
  100. Maeda RK, Karch F. 99.  2006. The ABC of the BX-C: the bithorax complex explained. Development 133:1413–22 [Google Scholar]
  101. Margueron R, Justin N, Ohno K, Sharpe ML, Son J. 100.  et al. 2009. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461:762–67 [Google Scholar]
  102. Marquardt S, Raitskin O, Wu Z, Liu F, Sun Q, Dean C. 101.  2014. Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription. Mol. Cell 54:156–65 [Google Scholar]
  103. McHugh CA, Chen CK, Chow A, Surka CF, Tran C. 102.  et al. 2015. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 521:232–36 [Google Scholar]
  104. Meier K, Brehm A. 103.  2014. Chromatin regulation: How complex does it get?. Epigenetics 9:1485–95 [Google Scholar]
  105. Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D. 104.  et al. 2002. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol. Cell 10:1107–17 [Google Scholar]
  106. Min J, Zhang Y, Xu RM. 105.  2003. Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev 17:1823–28 [Google Scholar]
  107. Molitor A, Latrasse D, Zytnicki M, Andrey P, Houba-Herin N. 106.  et al. 2016. The Arabidopsis hnRNP-Q Protein LIF2 and the PRC1 subunit LHP1 function in concert to regulate the transcription of stress-responsive genes. Plant Cell 28:2197–211 [Google Scholar]
  108. Morey L, Pascual G, Cozzuto L, Roma G, Wutz A. 107.  et al. 2012. Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells. Cell Stem Cell 10:47–62 [Google Scholar]
  109. Morisaki T, Muller WG, Golob N, Mazza D, McNally JG. 108.  2014. Single-molecule analysis of transcription factor binding at transcription sites in live cells. Nat. Commun. 5:4456 [Google Scholar]
  110. Muller J, Hart CM, Francis NJ, Vargas ML, Sengupta A. 109.  et al. 2002. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell 111:197–208 [Google Scholar]
  111. Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T. 110.  et al. 2002. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol. Cell 10:1119–28 [Google Scholar]
  112. Obersriebnig MJ, Pallesen EM, Sneppen K, Trusina A, Thon G. 111.  2016. Nucleation and spreading of a heterochromatic domain in fission yeast. Nat. Commun. 7:11518 [Google Scholar]
  113. Okulski H, Druck B, Bhalerao S, Ringrose L. 112.  2011. Quantitative analysis of polycomb response elements (PREs) at identical genomic locations distinguishes contributions of PRE sequence and genomic environment. Epigenet. Chromatin 4:4 [Google Scholar]
  114. Olariu V, Lövkvist C, Sneppen K. 113.  2016. Nanog, Oct4 and Tet1 interplay in establishing pluripotency. Sci. Rep. 6:25438 [Google Scholar]
  115. O'Loghlen A, Munoz-Cabello AM, Gaspar-Maia A, Wu HA, Banito A. 114.  et al. 2012. MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. Cell Stem Cell 10:33–46 [Google Scholar]
  116. Palazzo AF, Lee ES. 115.  2015. Non-coding RNA: What is functional and what is junk?. Front. Genet. 6:2 [Google Scholar]
  117. Pandya-Jones A, Bhatt DM, Lin CH, Tong AJ, Smale ST, Black DL. 116.  2013. Splicing kinetics and transcript release from the chromatin compartment limit the rate of Lipid A-induced gene expression. RNA 19:811–27 [Google Scholar]
  118. Pasini D, Hansen KH, Christensen J, Agger K, Cloos PA, Helin K. 117.  2008. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2. Genes Dev 22:1345–55 [Google Scholar]
  119. Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A. 118.  et al. 2010. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res 38:4958–69 [Google Scholar]
  120. Peng JC, Valouev A, Swigut T, Zhang J, Zhao Y. 119.  et al. 2009. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139:1290–302 [Google Scholar]
  121. Petruk S, Sedkov Y, Riley KM, Hodgson J, Schweisguth F. 120.  et al. 2006. Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell 127:1209–21 [Google Scholar]
  122. Phillips RK, Theriot J, Orme N. 121.  2008. Physical Biology of the Cell New York: Garland Sci. [Google Scholar]
  123. Piunti A, Shilatifard A. 122.  2016. Epigenetic balance of gene expression by Polycomb and COMPASS families. Science 352:aad9780 [Google Scholar]
  124. Portoso M, Ragazzini R, Brencic Z, Moiani A, Michaud A. 123.  et al. 2017. PRC2 is dispensable for HOTAIR-mediated transcriptional repression. EMBO J 36:981–94 [Google Scholar]
  125. Proudfoot NJ. 124.  2016. Transcriptional termination in mammals: stopping the RNA polymerase II juggernaut. Science 352:aad9926 [Google Scholar]
  126. Rank G, Prestel M, Paro R. 125.  2002. Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch. Mol. Cell. Biol. 22:8026–34 [Google Scholar]
  127. Ray P, De S, Mitra A, Bezstarosti K, Demmers JA. 126.  et al. 2016. Combgap contributes to recruitment of Polycomb group proteins in Drosophila. PNAS 113:3826–31 [Google Scholar]
  128. Reynolds N, Salmon-Divon M, Dvinge H, Hynes-Allen A, Balasooriya G. 127.  et al. 2012. NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression. EMBO J 31:593–605 [Google Scholar]
  129. Rickels R, Hu D, Collings CK, Woodfin AR, Piunti A. 128.  et al. 2016. An evolutionary conserved epigenetic mark of Polycomb Response Elements implemented by Trx/MLL/COMPASS. Mol. Cell 63:318–28 [Google Scholar]
  130. Riising EM, Comet I, Leblanc B, Wu X, Johansen JV, Helin K. 129.  2014. Gene silencing triggers polycomb repressive complex 2 recruitment to CpG islands genome wide. Mol. Cell 55:347–60 [Google Scholar]
  131. Ringrose L. 130.  2007. Polycomb comes of age: genome-wide profiling of target sites. Curr. Opin. Cell Biol. 19:290–97 [Google Scholar]
  132. Ringrose L, Howard M. 131.  2017. Dissecting chromatin-mediated gene regulation and epigenetic memory through mathematical modelling. Curr. Opin. Syst. Biol. 3:7–14 [Google Scholar]
  133. Ringrose L, Paro R. 132.  2004. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38:413–43 [Google Scholar]
  134. Ringrose L, Rehmsmeier M, Dura JM, Paro R. 133.  2003. Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster. Dev. Cell 5:759–71 [Google Scholar]
  135. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X. 134.  et al. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–23 [Google Scholar]
  136. Rozovskaia T, Tillib S, Smith S, Sedkov Y, Rozenblatt-Rosen O. 135.  et al. 1999. Trithorax and ASH1 interact directly and associate with the trithorax group-responsive bxd region of the Ultrabithorax promoter. Mol. Cell. Biol. 19:6441–47 [Google Scholar]
  137. Sanchez C, Sanchez I, Demmers JA, Rodriguez P, Strouboulis J, Vidal M. 136.  2007. Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor. Mol. Cell. Proteom. 6:820–34 [Google Scholar]
  138. Sanchez-Elsner T, Gou D, Kremmer E, Sauer F. 137.  2006. Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science 311:1118–23 Retraction 2014. Science 344:981 [Google Scholar]
  139. Sanchez-Herrero E, Akam M. 138.  1989. Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. Development 107:321–29 [Google Scholar]
  140. Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK. 139.  et al. 2010. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465:243–47 [Google Scholar]
  141. Schmitges FW, Prusty AB, Faty M, Stutzer A, Lingaraju GM. 140.  et al. 2011. Histone methylation by PRC2 is inhibited by active chromatin marks. Mol. Cell 42:330–41 [Google Scholar]
  142. Schmitt S, Prestel M, Paro R. 141.  2005. Intergenic transcription through a polycomb group response element counteracts silencing. Genes Dev 19:697–708 [Google Scholar]
  143. Schoeftner S, Sengupta AK, Kubicek S, Mechtler K, Spahn L. 142.  et al. 2006. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J 25:3110–22 [Google Scholar]
  144. Schwartzman O, Tanay A. 143.  2015. Single-cell epigenomics: techniques and emerging applications. Nat. Rev. Genet. 16:716–26 [Google Scholar]
  145. Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V. 144.  2007. Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA 13:223–39 [Google Scholar]
  146. Simon J, Chiang A, Bender W, Shimell MJ, O'Connor M. 145.  1993. Elements of the Drosophila bithorax complex that mediate repression by Polycomb group products. Dev. Biol. 158:131–44 [Google Scholar]
  147. Sing A, Pannell D, Karaiskakis A, Sturgeon K, Djabali M. 146.  et al. 2009. A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell 138:885–97 [Google Scholar]
  148. Smith ER, Lee MG, Winter B, Droz NM, Eissenberg JC. 147.  et al. 2008. Drosophila UTX is a histone H3 Lys27 demethylase that colocalizes with the elongating form of RNA polymerase II. Mol. Cell. Biol. 28:1041–46 [Google Scholar]
  149. Smith ST, Petruk S, Sedkov Y, Cho E, Tillib S. 148.  et al. 2004. Modulation of heat shock gene expression by the TAC1 chromatin-modifying complex. Nat. Cell Biol. 6:162–67 [Google Scholar]
  150. Sneppen K. 149.  2014. Models of Life Cambridge, UK: Cambridge Univ. Press [Google Scholar]
  151. Sneppen K. 150.  2017. Models of life: epigenetics, diversity and cycles. Rep. Prog. Phys. 80:042601 [Google Scholar]
  152. Sneppen K, Dodd IB. 151.  2012. A simple histone code opens many paths to epigenetics. PLOS Comput. Biol. 8:e1002643 [Google Scholar]
  153. Sneppen K, Dodd IB. 152.  2016. Nucleosome dynamics and maintenance of epigenetic states of CpG islands. Phys. Rev. E 93:062417 [Google Scholar]
  154. Steffen PA, Fonseca JP, Gänger C, Dworschak E, Kockmann T. 153.  et al. 2013. Quantitative in vivo analysis of chromatin binding of Polycomb and Trithorax group proteins reveals retention of ASH1 on mitotic chromatin. Nucleic Acids Res 41:5235–50 [Google Scholar]
  155. Steffen PA, Fonseca JP, Ringrose L. 154.  2012. Epigenetics meets mathematics: towards a quantitative understanding of chromatin biology. BioEssays 34:901–13 [Google Scholar]
  156. Steffen PA, Ringrose L. 155.  2014. What are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory. Nat. Rev. Mol. Cell Biol. 15:340–56 [Google Scholar]
  157. Tanaka Y, Katagiri Z, Kawahashi K, Kioussis D, Kitajima S. 156.  2007. Trithorax-group protein ASH1 methylates histone H3 lysine 36. Gene 397:161–68 [Google Scholar]
  158. Tanay A, Regev A. 157.  2017. Scaling single-cell genomics from phenomenology to mechanism. Nature 541:331–38 [Google Scholar]
  159. Thakore PI, Black JB, Hilton IB, Gersbach CA. 158.  2016. Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nat. Methods 13:127–37 [Google Scholar]
  160. Tie F, Banerjee R, Conrad PA, Scacheri PC, Harte PJ. 159.  2012. Histone demethylase UTX and chromatin remodeler BRM bind directly to CBP and modulate acetylation of histone H3 lysine 27. Mol. Cell. Biol. 32:2323–34 [Google Scholar]
  161. Tie F, Banerjee R, Fu C, Stratton CA, Fang M, Harte PJ. 160.  2016. Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain. PNAS 113:E744–53 [Google Scholar]
  162. Tie F, Banerjee R, Saiakhova AR, Howard B, Monteith KE. 161.  et al. 2014. Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing. Development 141:1129–39 [Google Scholar]
  163. Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V. 162.  et al. 2009. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136:3131–41 [Google Scholar]
  164. Van Aller GS, Pappalardi MB, Ott HM, Diaz E, Brandt M. 163.  et al. 2014. Long residence time inhibition of EZH2 in activated Polycomb Repressive Complex 2. ACS Chem. Biol. 9:622–29 [Google Scholar]
  165. van Heeringen SJ, Akkers RC, van Kruijsbergen I, Arif MA, Hanssen LL. 164.  et al. 2014. Principles of nucleation of H3K27 methylation during embryonic development. Genome Res 24:401–10 [Google Scholar]
  166. Voigt P, LeRoy G, Drury WJ 3rd, Zee BM, Son J. 165.  et al. 2012. Asymmetrically modified nucleosomes. Cell 151:181–93 [Google Scholar]
  167. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P. 166.  et al. 2004. Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873–78 [Google Scholar]
  168. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R. 167.  et al. 2011. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–24 [Google Scholar]
  169. Wang L, Brown JL, Cao R, Zhang Y, Kassis JA, Jones RS. 168.  2004. Hierarchical recruitment of polycomb group silencing complexes. Mol. Cell 14:637–46 [Google Scholar]
  170. Wang X, Goodrich KJ, Gooding AR, Naeem H, Archer S. 169.  et al. 2017. Targeting of Polycomb Repressive Complex 2 to RNA by short repeats of consecutive guanines. Mol. Cell 65:1056–67.e5 [Google Scholar]
  171. Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE. 170.  2010. A region of the human HOXD cluster that confers polycomb-group responsiveness. Cell 140:99–110 [Google Scholar]
  172. Wu X, Johansen JV, Helin K. 171.  2013. Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol. Cell 49:1134–46 [Google Scholar]
  173. Xiao B, Wilson JR, Gamblin SJ. 172.  2003. SET domains and histone methylation. Curr. Opin. Struct. Biol. 13:699–705 [Google Scholar]
  174. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L. 173.  et al. 2010. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol. Cell 38:662–74 [Google Scholar]
  175. Yu M, Mazor T, Huang H, Huang HT, Kathrein KL. 174.  et al. 2012. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol. Cell 45:330–43 [Google Scholar]
  176. Yuan G, Ma B, Yuan W, Zhang Z, Chen P. 175.  et al. 2013. Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases. J. Biol. Chem. 288:30832–42 [Google Scholar]
  177. Yuan W, Wu T, Fu H, Dai C, Wu H. 176.  et al. 2012. Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science 337:971–75 [Google Scholar]
  178. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. 177.  2011. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J. Biol. Chem. 286:7983–89 [Google Scholar]
  179. Zhan H, Stanciauskas R, Stigloher C, Dizon KK, Jospin M. 178.  et al. 2014. Invivo single-molecule imaging identifies altered dynamics of calcium channels in dystrophin-mutant C. elegans. Nat. Commun. 5:4974 [Google Scholar]
  180. Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ. 179.  et al. 2010. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol. Cell 40:939–53 [Google Scholar]
  181. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. 180.  2008. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322:750–56 [Google Scholar]
  182. Zhao R, Nakamura T, Fu Y, Lazar Z, Spector DL. 181.  2011. Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation. Nat. Cell Biol. 13:1295–304 [Google Scholar]
  183. Zhou J, Ashe H, Burks C, Levine M. 182.  1999. Characterization of the transvection mediating region of the Abdominal-B locus in Drosophila. Development 126:3057–65 [Google Scholar]
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